The Golden research group uses synthetic medicinal chemistry to address issues in chemical biology. We develop synthetic methodology to generate new chemical architecture and explore its associated pharmacology. Currently, projects in the Golden laboratory focus on chemical methodology development and the optimization of anti-infective and anticancer agents in cell and animal models. We work closely with expert collaborators who assess our compounds against various biological targets, and through structural manipulation of our chemical scaffolds, we refine properties to achieve a desired activity profile. Several projects are underway, and a few are represented below.
Project 1: Exploration of a novel quinazolinone rearrangement
We discovered that alpha-chloromethylquinazolinones, when treated with acyclic diamines, rearrange to form amidines. We explored the scope of this reaction as it relates to the electronics governing the susceptibility of the quinazolinone core to rearrange under multiple conditions. We further adapted the transformation to include the conversion of extended BOC-protected amino acids to the desired amidines through an efficient, telescoped sequence that integrates at least five chemical transformations in one pot!
Project 2: Development of anti-alphaviral agents with in vivo efficacy
Alphaviruses, RNA viruses spread most commonly by infected mosquitoes, can cause significant disease in animals and humans ranging from fever, rash, persistent arthritis, encephalitis and death. Though several of these agents are classified as bioterrorism threats, there are no FDA approved vaccines or drugs available for any alphavirus infection. Our laboratory has developed several compound classes that show efficacy against select alphaviruses in cells and in mice.
Project 3: Development of broad spectrum antiparasitic compounds
Our group has discovered three distinct structural classes that show broad spectrum inhibition of parasites related to malaria, African sleeping sickness and leishmaniasis. We have defined preliminary structure-activity relationships around each class and are now prepared to derive improved inhibitors for more advanced in vivo studies.